title: PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.
abstract: OBJECTIVE
  The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP).
  
  
  BACKGROUND
  Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context.
  
  
  METHODS
  A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years.
  
  
  RESULTS
  At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all).
  
  
  CONCLUSIONS
  Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952).
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Huelsmann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Neuhold
authors.forename: Michael
authors.initials: M
authors.lastname: Resl
authors.forename: Guido
authors.initials: G
authors.lastname: Strunk
authors.forename: Helmut
authors.initials: H
authors.lastname: Brath
authors.forename: Claudia
authors.initials: C
authors.lastname: Francesconi
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.forename: Rudolf
authors.initials: R
authors.lastname: Prager
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
authors.forename: Martin
authors.initials: M
authors.lastname: Clodi
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D006339:Heart Rate; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011322:Primary Prevention; D011446:Prospective Studies
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: ACE; N-terminal pro–B-type natriuretic peptide; NT-BNP-selected; NT-proBNP; RAS; RAS antagonists; angiotensin-converting enzyme; beta-blockers; diabetes mellitus; eGFR; estimated glomerular filtration rate; primary prevention; renin-angiotensin system